Treatment of excessive sebaceous glands secretion with substituted cysteamine compounds

ABSTRACT

A process of treating acne with a composition containing substituted cysteamine compounds.

United States Patent Kalopissis 1451 June 20, 1972 Inventor:

Assignee:

Gregoire Kalopissis, Paris, France Societe Anonyme dite:-L'0real, Paris,

France Filed:

Appl. No.:

Sept. 15, 1969 Related U.S. Application Data Continuation-impart of Ser. No. 736,960, June 14, 1968, abandoned, Continuation-impart of Ser. No. 801,840, Feb. 24, 1969.

Foreign Application Priority Data Jan. 29, 1964 Dec. 22, 1965 June 21, l967 July 28, 1967 Feb. 23, 1968 April I9, 1968 June 3, I969 France ..64 147202 I Luxembourg ..5 555 3 France.. ....67l560250 France ..67949l3 Luxembourg... .....55553 Luxembourg.... .....55935 [52] U.S. Cl ..424/330, 424/75, 424/230, 424/263, 424/264, 424/275, 424/280, 424/316, 424/3l9, 424/324, 424/325, 424/329 [51] Int. Cl. ..A6lk 27/00 [58] Field ofSearch ..424/330 [56] References Cited UNITED STATES PATENTS 2,769,839 11/1956 Fincke' ..260/570.5 2,835,704 5/1958 Walton ..260/562 FOREIGN PATENTS OR APPLICATIONS 1,085,513 7/1954 France 260/501 l 2 79,717 1 l/l955 Netherlands ..260/56l S Primary Examiner-Albert T. Meyers Assistant Examiner-Vera C. Clarke Attorney-Holcombe, Wetherill & Brisebois [57] ABSTRACT A process of treating acne with a composition containing substituted cysteamine compounds.

2 Claims, No Drawings TREATMENT OF EXCESSIVE SEBACEOUS GLANDS SECRETION WITH SUBSTITUTED CYSTEAMINE COMPOUNDS This application is a continuation-in-part of application Ser. No. 736,960, filed June 14, 1968, now abandoned, and application Ser. No. 801,840, filed Feb. 24, 1969.

SUMMARY OF THE INVENTION The present invention relates to new composition and to a new process for diminishing excessive secretions by the sebaceous glands of the skin.

It is known that in certain cases the sebaceous glands of the skin produce excessive secretions which lead to an objectional appearance, and may lead in some cases to certain forms of acne. The invention is based on the discovery that certain compositions are useful in diminishing such excessive secretions and that these compositions are also useful in treating acne.

It is the object of the present invention to provide a new cosmetic composition which may be applied to the skin to diminish excessive secretion of the sebaceous glands. This composition is characterized by the fact that it contains in a suitable cosmetic vehicle at least one active compound selected from the group consisting of the S-substltuted derivative of cysteine and the S-substituted derivative of cysteamine.

Among the active compounds which may be used in the above-defined compositions are:

1. Those compounds corresponding to the following formu- 1a:

in which R is selected from the group consisting of (C l-l C-, (C l- Q2 CH, C, H, CH and HOOC(CH in which nrepresents a whole number equal to or less than 4, and preferably 1 or 2.

These compounds may be used in the form of their mineral or organic acid salts, or in an esterified form, by an alcohol having up to six carbon atoms.

A hydrogen atom from the amine function may be replaced by a -COR or SO R' radical, in which R represents an alkyl group having up to six carbon atoms or an aryl radical, such as 3-pyridyl, phenyl substituted by CH;,, alkoxy radical, acetamido radical or an aralkyl radical.

2. Those compounds corresponding to the following formula: VA

1 Rzr-S-f-(C H2) w-CHz-NH,

gt; M

in which or the 2-thienyl radical: v

or the 2-( N-oxypyridyl)radical The compounds of this group are preferably used in the form of their salt with a mineral or inorganic acid, such for example as the halohydric acids, salicylic acid, para-toluenesulfonic acid, citric acid, phosphoric acid, malic acid, tartaric acid, nicotinic acid, or ascorbic acid. Compounds of this type; which have a carboxylic group may advantageously be esterified to increase their liposolubility.

A hydrogen atom from the amine functions of the compounds of this group may be replaced by a --COR' radical or an SO R, radical in which R represents a lower alkyl or aryl radical.

. 3. The compounds corresponding to the following formula:

RSCH -CH NH, 111 in which Rrepresents a hydrocarbon radical having up to 20 carbon atoms, which may be saturated or unsaturated and have a branched or linear chain, and may comprise one or rnore heteros forms and one or more alcohol groups, one of which may be terminal.

R may be an alkyl such as Cl-l C H -C H an alkenyl such as --C H C H C H a heterocyclic group such as o -C H NH,

R2 NIH-R4 in which n 0 or 1, R and R may be identical or different and are selected from the group consisting of a hydrogen atom and a lower alkyl radical having 1 to 3 carbon atoms. R represents a group corresponding to the formula 2 (CH ),,R,, (in which p is equal to 0, l or 2) and in which R represents COOR (R representinga lower alkyl radical),

( R, representing a hydrogen atom or an acyl or sulfonyl radical, R, represents a lower alkyl radical or a hydrogen atom only when R represents a hydrogen atom),

- the 2-thienyl radical having the formula:

- the 2-pyridyl radical, -the 2-(N-oxypyridyl) radical having the formula: H

R, represents a --(CH,),,,Cl-l0, radical, in which m is a whole number from 1 to 5 inclusive, and y= 1 and r 1, if R, does not include a free amine group, y= 2 and x= 1, if R, does include a free amine group, or an acyl or sulfonyl radical, in which case R, may be:

- (C,H,),C, (C,H,),CH--, or C,H,-CH,--, in which case: F l and x= I, if R, does not include a free amine group,

' and F 2 and x= 1, if R, does include a free amine group, -(CH=)- C0,H, in which case y= l and 1, if R, includes a free amine group, F l and F 2, if R, does not include a-free amine group. In all of the above cases in which the active compound comprises a free carboxylic acid group, this 'may take the form of a complex with a cationic quaternary ammonium bactericide, such for example as [diisobutylphenoxyethoxyethyl dimethyl benzyl1- ammonium chloride monohydrate or [diisobutyl cresoxyethoxyethyl dimethyl benzyl] ammonium chloride monohydrate. v v

Among: the active compounds corresponding to the above formulas are:

- S-trityl-l-cysteine having the formula:

and its hydrochloride, S-(2(carboxyethyD-l-cysteine having the formula:

and its hydrochloride,

- S-(carboxymethyl) cysteamine having the formula:

HOOC CH, S CH, CH, NH, and its hydrochloride,

- S-tritylcysteamine having the formula: (C,H,), C S

CH, CH, NH, and its hydrochloride,

- S-benzy'lcysteamine hydrochloride having the formula:

C,H, CH, S CH, CH, NH, HCI

- (3- B- aminoethylthio-Z-hydroxy) propyltrimethylammonium hydrochloride having the formula: (CH,), Nf CH, CHOH CH, S CH,

CH, -NH,, HCI S-(carboxymethyD-methyl cysteinate having the formula:

HOOCCH2-SCH2CHCOOCHZ S-(met'hoxycarbonylmethyl) cysteine having the formula:

nae-o0 o-om-s-cm-on-o 0 OH and its hydrochloride,

- N-acetyl-S-benzylcysteamine having the formula:

-S-benzylcyste'amine dicitrate having the formula:

- S-benzylcysteamine salicylate having the formula:

-'S-benzylcysteamine p-toluenesulfonate having the formu- S benzylcysteamine nicotinate having the formula:

- S-benzylcysteamine hydrobromide having the formula:

CJ-l, CH, S CH, CH, NH, HBr S-benzylcysteamine ditartrate having the formula:

, -S-benzyIcysteamine malate having the formula: C,H, CH,--S-CH,CH,NH, H0,CCH,'CHOHCO, H the diacid phosphate of S-benzylcysteamine having the formula: C,H, CH, S CH, CH, NH, H,PO, S-thienylcysteamine having the formula:

and its hydrochloride,

3,671,643 a 7 I g.

- 2-acetamido-4-thia-nonanedioate of 2,2-thio-bis m iron oxide 0.3

(ethylamine), having the formula:- z fgi z 'g ggfi I HN CH2 CHS CH CH NH' Q t l r l i l h l a 'th 15 I HOzC-(CHzh-S-CHz-CH-C 0 H ,,f;;{,; y 5 7 H Silicone oil I g 00 3 Polyglycolstearate Para-hydrobenzoic acid ester 0.20g S-acetamido-3-thra-hexanedroate of di-(2-benzylthlo- Water, q.s.p. I00 g ethylamine), having the formula: l0

(CtH --C H2 S -CHs-C H2NHa)2, I EXAMPLE 4 0 s H 20 GET-CH 00211 A milk is prepared by mixing together the following Ill- E a gredients:

v The composition according to the invention is preferably smitylcymmine hydrochloride 2 8 used in the form of a cream, milk, gel, dermatological cake, or ma-m polygc ylic i sold commercially an aerosol foam It may also take the form of an aqueous or under the trademark CARBOPOL 934 0.375 g hydroalcoholic lotion. L' SE ""3? 1'': "fig' g t r f h lane l 5 The composition according to the invention will ordinarily 1.5:? y 6 m o o e y 8 contain Percent of thc active compound 35 abolm Cetyl stearyl alcoholoxyethylenated with. 16 moles defined. of ethylene oxide 3 g The composition according to the invention may also con- 23:2: m rim") 2 5 tain any of the conventional ingredients of facial creams such Tmmohffinfl, y PH 8 as greases, emulsifiers, preservatives, perfumes, dyes and 25 Preservative based on propyl para'hydroxybenloate waxes 7 'sold commercially under the trademark They may also contain colored pigments which make it igfi; v :88:

possible to tint the skinand to mask esthetic'defects of the skin, while the active products reduce the excessive activity of v the sebaceous glands. 3o EXAMPLE 5 It is a further object of the present invention to provide a new. method of diminishing excessive secretion by the. is P p y mixing the followi"! sebaceous glands of the skin in order to reduce acne, which E'Qdiems: method is characterized by the fact that a composition such as I defined above is applied to the surfaces to be treated. g lgtzfizfy fi y 015 I In. order that the fl" may bc t "f f ethoxyethyldimethyl-benzyl] ammonium chloride 0.75 g several examples of composit ons embodying the invention m (tri gh nolg i 9 cc will now be given, purely by way of example. j lggrt'ulmeh l g o a co 0 I EXAMPLE 1 40 I Water q.s.p. l 100 g An anti-acne cream for use on the face is prepared by mixing together: I I r EXAMPLE 6 s b i I t h dmcmm. 1 An anti-acne lotion is prepared which is identical to the one a lco hzl oxryethylen ated with 5 described in Example 12 except that the cationic quaternary l5 moles of ethylene oxide 7 g ammonium bactericide is replaced by hexachlorophene. Siliconeoil l g I (dimethylpolysiloxane having a viscosity of g EXAMPLE 7.

-20-22 centipnises at room temperature) I Diethylene glycol stearate, 6 a An anti-acne foaming gel is prepared by mixing the follow- Preservative containing methyl parain: ingredients. p

, hydroxybenzoateGsold commercially under the o lo g trademark NlPA [NE g Preservative containing propyl para- Reticulated polyacrylic acid sold under the hydrosybenzoate sold commercially under the trademark CARBOPOL 934 25 g trademark NIPASOL g Sulfates of fatty alcohol (magnesium ethoxylauryl Water, q.s.p. j ll cc sulfate) 8 g Polyglycol (glycerol) V [0 g Ammonia v 0.2 g 1 S-carboxymethyl cysteine 2 g I 7 EXAMPLE 2 v Water, q.s.p. 7 I00 g An anti-acne cream is prepared by mixing the following 1 constituents: EXAMPLE 8 gl z y l l a y g giif a ah mol" 2 l An anti-acne aerosol foam is prepared by mixing the followeysearyacoooxye y e l of ethylene oxide v "1 n; Ingredients In an aerosol bomb. Silicone oil g g Y Polyglycol stearate 6 l v Reticulated polyacrylic acid sold underthe alara-hydroxybenzoic acid ester I trademark CARBOI'OL 934 25 g ater, q.s.p. I Sulfate: of fatty alcohol 8 g (magnesium ethoxylauryl sulfates) Polyglyeol (glycerol) 10 g Ammonia 0.2 g EXAMPLE 3 S-carboxymethyl cysteine 2 g A masking cream designed to treatacne while masking the q -P- 100 s blackheads is prepared by mixing thefollowing ingredients:

- 88 g of the above solution is packaged in an aerosol can with S-benzylcysteamine hydrochloride 2 g 18 zfigllfluomdlchlommamane- Titanium oxide 10 g l. A method of treating the human skin to diminish excessive secretion by thesebaceous glands comprising applying to the skin so characterized in amounts effective to diminish said excessive secretion a composition comprising an aqueous solution of, as an active ingredient, a compound having the formula 

2. The method of claim 1 wherein said active ingredient is S-benzylcysteamine. 